Erratum: Superfluid and Supersolid Phases of

This corrects the article DOI: 10.1103/PhysRevLett.124.205301.

Superfluid and Supersolid Phases of

We revisited the phase diagram of the second layer of ^{4}He on top of graphite using quantum Monte Carlo methods. Our aim was to explore the existence of the novel phases suggested recently in experimental works, and determine their properties and stability limits. We found evidence of a superfluid quantum phase with hexatic correlations, induced by the corrugation of the first Helium layer, and a quasi-two-dimensional supersolid corresponding to a 7/12 registered phase. The 4/7 commensurate solid was found to be unstable, while the triangular incommensurate crystals, stable at large densities, were normal.

Impact of pre-radiation therapy quality of life in lung cancer survival: a prospective, intention-to-treat, multicenter study.

PURPOSE: Lung cancer (LC) has a significant impact on patients' health-related quality of life (HRQoL). We investigate the correlations between pre-radiation therapy HRQoL and survival. MATERIALS AND METHODS: A prospective, intention-to-treat, multicentre study of 437 patients with LC recruited at the radiation oncology departments of three different institutions was conducted between 2012 and 2016. QoL was assessed using the EORTC-QLQ-C30 (v3.0) and EORTC-QLQ-LC13 questionnaires. Global health status (GHS), physical (PF), role functioning (RF), emotional (EF), cognitive (CF), and social functioning (SF) as well as symptoms scores were evaluated in univariate and multivariate analyses. RESULTS: The cohort consisted of 376 men (86%) and 61 women, with a median age of 66 years (range 31-88). Histology was: 72% (n = 315) non-small cell lung cancer and 28% small cell lung cancer. The most common stage was III (80%) and the median follow-up for alive patients was 30 months (range 7-76). Multivariate analysis showed that RF was associated with a lower risk of mortality (HR: 0.693; p = 0.008) and recurrence (HR: 0.737; p = 0.040). Additionally, lower scores on EF and PF were associated with higher mortality (HR: 0.696; p = 0.003 and HR: 0.765; p = 0.044, respectively). Appetite loss, constipation, and dysphagia were associated with a higher risk of mortality (HR: 1.985; p < 0.001, HR: 1.373; p = 0.036, and HR: 1.659; p = 0.002, respectively), while appetite loss was the only symptom associated with a higher risk of recurrence (HR: 1.525; p = 0.014). CONCLUSIONS: Pre-radiation therapy scores on RF, EF, and PF and symptoms like appetite loss, dysphagia, and constipation were associated with the risk of mortality. This information could be added to other prognostic factors to guide our treatment decisions.

Dinophysis Species and Diarrhetic Shellfish Toxins: 20 Years of Monitoring Program in Andalusia, South of Spain.

In Andalusia, the official monitoring program for toxic phytoplankton and marine biotoxins was launched in 1994 to comply with European legislation. Since then, there have been numerous episodes of DST (Diarrhetic shellfish toxins) associated with the proliferation of Dinophysis species. This article reviews two decades of time series data and assesses the effectiveness of the program established. The testing of lipophilic toxins and toxic phytoplankton is based on official methods harmonized and accredited since 2007 according to the standard UNE-EN-ISO 17025. The major species of Dinophysis identified were D. acuminata complex, D. caudata, D. acuta and D. fortii, with the main growth season being from early spring until the end of autumn. Both D. acuminata complex and D. acuta have been clearly associated with toxicity in molluscs. Despite the complexity of data obtained through monitoring programs, it is possible to provide early warning of potential health risks for most situations. This is the first report of Dinophysis species and their relation to DST events in a time series from Andalusia.

Cardiovascular disease and survival in non-small cell lung cancer: a multicenter prospective assessment.

PURPOSE: Chronic inflammation contributes to cancer development via multiple mechanisms. We hypothesized that cardiovascular diseases (CVD) are also an independent risk factor for survival in non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Prospective multicenter data from 345 consecutive NSCLC patients treated from January 2013 to January 2017 were assessed. Median follow-up for all patients was 13 months (range 3-60 months). There were 109 patients with baseline heart disease (HD 32%), 149 with arterial hypertension (43%), 85 with diabetes mellitus (25%), 129 with hyperlipidemia (37%) and 45 with venous thromboembolism events (VTE 13%). A total of 289 patients (84%) were treated with platinum-based chemotherapy (CT), 300 patients (87%) received thoracic radiation therapy (RT; median radiation dose: 60 Gy [range 12-70]); and 50 (15%) patients underwent surgery. RESULTS: Our cohort consisted of 305 men (88%) and 40 (12%) women, with a median age of 67 years (range 31-88 years). Seventy percent had a Karnofsky performance status (KPS) ≥ 80. Multivariate analyses showed a lower OS and higher risk of distant metastasis in patients with advanced stages (p = 0.05 and p < 0.001, respectively) and HD (HR 1.43, p = 0.019; and HR 1.49, p = 0.025, respectively). Additionally, patients with VTE had lower local control (HR 1.84, p = 0.025), disease-free survival (HR 1.64, p = 0.020) and distant metastasis-free survival (HR 1.73, p = 0.025). CONCLUSIONS: HD and VTE are associated with a higher risk of mortality and distant metastasis in NSCLC patients. Chronic inflammation associated with CVDs could be an additional pathophysiologic factor in the development of distant metastasis.

Validation of a Spanish Version of the Information Needs in Cardiac Rehabilitation Scale to Assess Information Needs and Preferences in Cardiac Rehabilitation.

BACKGROUND: The identification of information needs is considered the first step to increase knowledge that ultimately could improve health outcomes in cardiac rehabilitation (CR). OBJECTIVE: The aim of this study was to psychometrically validate the Spanish Information Needs in Cardiac Rehabilitation (INCR). METHODS: The Spanish INCR was psychometrically tested in 184 patients undergoing CR. The internal consistency was assessed using Cronbach α, factor structure was assessed using exploratory factor analysis, and criterion validity regarding educational level, occupation, and duration in CR was assessed. RESULTS: Cronbach α was .97. Factor analysis revealed 10 factors, all internally consistent. Criterion validity was supported by significant differences in total INCR scores by educational level (P < .01), occupation (P < .01), and duration in CR (P < .05). Emergency/safety was the greatest information need perceived by patients. CONCLUSIONS: The Spanish INCR was demonstrated to have good reliability and validity. This tool can be applicable in clinical and research settings, assessing patients' information needs during CR and as part of education programming.

Keratitis secondary to Fusarium spp. in Spain 2012-2014. / Queratitis secundaria a Fusarium spp. en España 2012-2014.

OBJECTIVE: To describe the clinical-epidemiological characteristics of a case series of fungal keratitis associated with Fusarium spp.., in Spain during the years 2012 to 2014. METHODS: A retrospective study of a case series was conducted on a systematic random sample of 10% of patients identified in Health Centres of provincial capitals (n=250). The centres were asked whether they had been presented with cases of Fusarium spp. keratitis characterised by microbiological methods. Of the 23 centres that responded, 14 had detected cases, with 13 of them accepting to participate, and 11 of them completing the study. The latter being sent a previously validated questionnaire. The variables analysed were: age, gender, habitual residence, profession, disease and medical history (previous systemic and ocular diseases, previous eye surgeries), and their outcomes. RESULTS: The response rate was 92%, identifying 23 cases of Fusarium spp.. of which 21 (91.3%) of them lived in urban areas. The professions most affected by the disease included chefs, administrative, and technical, with 13 cases (56.5%). The treatment guidelines established to confirm the infection showed the combined use of topical antibiotics associated with antiviral and/or antifungal agents. The use of contact lenses (86.9%) was the main risk factor. DISCUSSION: This study showed that this is a rare disease in Spain, but that a large percentage of people who present with the disease are resident in urban areas, and they work in closed environments, focusing attention on microtraumas caused by use of contact lenses.

Novel giardicidal compounds bearing proton pump inhibitor scaffold proceeding through triosephosphate isomerase inactivation.

Giardiasis is a worldwide parasitic disease that affects mainly children and immunosuppressed people. Side effects and the emergence of resistance over current used drugs make imperative looking for new antiparasitics through discovering of new biological targets and designing of novel drugs. Recently, it has determined that gastric proton-pump inhibitors (PPI) have anti-giardiasic activity. The glycolytic enzyme, triosephosphate isomerase (GlTIM), is one of its potential targets. Therefore, we employed the scaffold of PPI to design new compounds aimed to increase their antigiardial capacity by inactivating GlTIM. Here we demonstrated that two novel PPI-derivatives (BHO2 and BHO3), have better anti-giardiasic activity than omeprazole in concentrations around 120-130 µM, without cytotoxic effect on mammal cell cultures. The derivatives inactivated GlTIM through the chemical modification of Cys222 promoting local structural changes in the enzyme. Furthermore, derivatives forms adducts linked to Cys residues through a C-S bond. We demonstrated that PPI can be used as scaffolds to design better antiparasitic molecules; we also are proposing a molecular mechanism of reaction for these novel derivatives.

Liquid and Solid Phases of

Recent heat-capacity experiments show quite unambiguously the existence of a liquid ^{3}He phase adsorbed on graphite. This liquid is stable at an extremely low density, possibly one of the lowest found in nature. Previous theoretical calculations of the same system, and in strictly two dimensions, agree with the result that this liquid phase is not stable and the system is in the gas phase. We calculated the phase diagram of normal ^{3}He adsorbed on graphite at T=0 using quantum Monte Carlo methods. Considering a fully corrugated substrate, we observe that at densities lower than 0.006 Å^{-2} the system is a very dilute gas that, at that density, is in equilibrium with a liquid of density 0.014 Å^{-2}. Our prediction matches very well the recent experimental findings on the same system. On the contrary, when a flat substrate is considered, no gas-liquid coexistence is found, in agreement with previous calculations. We also report results on the different solid structures, and on the corresponding phase transitions that appear at higher densities.

Application of EQ-5D-5L questionnaire in patients suffering from urinary incontinence. / Aplicación del cuestionario EQ-5D-5L en pacientes que padecen incontinencia urinaria.

BACKGROUND: Urinary incontinence is associated with reduced quality of life and given the high prevalence of people with this condition, it could be useful to know the impact of having urinary incontinence on physical, psychological and social aspects. The Spanish value set of EQ-5D was used to assign single scores to the EQ-5D-5L health states. EQ-5D-5L is a health-related quality of life questionnaire, which allows assessing health status. The aim of this study was to provide normative values of EQ-5D-5L in a population sample with urinary incontinence. STUDY DESIGN: Cross-sectional study. METHODS: A total of 965 people with urinary incontinence (297 men and 668 women) were included in this study. EQ-5D-5L index, VAS and health status are showed in the current study considering gender, age group, region, marital status, smoking status, net monthly incomes of household and educational level. RESULTS: Higher prevalence was observed in women (69.22%) compared with men (30.78%). Mean (SD) EQ-5D-5L utility index and VAS score were 0.58 (0.40) and 53.91 (22.16), respectively, for overall population. The 16.1% (155 people) reported perfect health status (11111). The utility equivalent to set values 55555 was not reported by anyone. CONCLUSION: This study provides normative values of EQ-5D-5L in a Spanish population sample with urinary incontinence.

Ecografía torácica / No disponible

Clásicamente relegada al estudio de la patología pleural, en los últimos años se han descrito numerosas aplicaciones de la ecografía en el estudio de diversas enfermedades del tórax que afectan no sólo a la pleura, sino también al pulmón, pared torácica o diafragma. Comparada con otras pruebas de imagen, la ecografía presenta importantes ventajas, entre las que se incluyen la ausencia de radiaciones ionizantes y la obtención de imágenes en tiempo real, además de su portabilidad y bajo coste. En el presente artículo, se resumen algunos aspectos técnicos básicos de la ecografía, los principales hallazgos ecográficos en el tórax normal, así como las diferentes aplicaciones de la técnica y los patrones ecográficos más comunes en patología torácica

No disponible

Punciones transtorácicas guiadas con ecografía / No disponible

La ecografía transtorácica es una técnica de gran utilidad para guiar punciones. Presenta ventajas sobre otras, como el TAC y la fluoroscopia. El mayor beneficio que el neumólogo puede encontrar en ella es la accesibilidad de la técnica y la visión en tiempo real de la aguja. Como cualquier otra, requiere de una curva de aprendizaje, que es perfectamente asumible por los neumólogos que se dedican a realizar técnicas neumológicas

No disponible

Association between single-nucleotide polymorphisms in DNA double-strand break repair genes and prostate cancer aggressiveness in the Spanish population.

BACKGROUND: Novel predictors of prognosis and treatment response for prostate cancer (PCa) are required to better individualize treatment. Single-nucleotide polymorphisms (SNPs) in four genes directly (XRCC5 (X-ray repair complementing defective repair in Chinese hamster cells 5) and XRCC6 (X-ray repair complementing defective repair in Chinese hamster cells 6)) or indirectly (PARP1 and major vault protein (MVP)) involved in non-homologous end joining were examined in 494 Spanish PCa patients. METHODS: A total of 22 SNPs were genotyped in a Biotrove OpenArray NT Cycler. Clinical tumor stage, diagnostic PSA serum levels and Gleason score at diagnosis were obtained for all participants. Genotypic and allelic frequencies were determined using the web-based environment SNPator. RESULTS: (XRCC6) rs2267437 appeared as a risk factor for developing more aggressive PCa tumors. Those patients carrying the GG genotype were at higher risk of developing bigger tumors (odds ratio (OR)=2.04, 95% confidence interval (CI) 1.26-3.29, P=0.004), present higher diagnostic PSA levels (OR=2.12, 95% CI 1.19-3.78, P=0.011), higher Gleason score (OR=1.65, 95% CI 1.01-2.68, P=0.044) and D'Amico higher risk tumors (OR=2.38, 95% CI 1.24-4.58, P=0.009) than those patients carrying the CC/CG genotypes. Those patients carrying the (MVP) rs3815824 TT genotype were at higher risk of presenting higher diagnostic PSA levels (OR=4.74, 95% CI 1.40-16.07, P=0.013) than those patients carrying the CC genotype. When both SNPs were analyzed in combination, those patients carrying the risk genotypes were at higher risk of developing D'Amico higher risk tumors (OR=3.33, 95% CI 1.56-7.17, P=0.002). CONCLUSIONS: We believe that for the first time, genetic variants at XRCC6 and MVP genes are associated with risk of more aggressive disease, and would be taken into account when assessing the malignancy of PCa.

Monitorización del tratamiento antibiótico nebulizado en bronquiectasias no fibrosis quística colonizadas por Pseudomonas aeruginosa. Estudio multicéntrico / Monitoring nebulized antibiotic treatment in non-cystic fibrosis bronchiectasis colonized by Pseudomonas aeruginosa: A multi-centerstudy

OBJETIVOS: 1- Valorar la adherencia al tratamiento nebulizado con colistimetato de sodio-Promixín® con dispositivo Ineb® en pacientes con bronquiectasias (BQ) no fibrosis quística (FQ) colonizadas por Pseudomonas aeruginosa; 2- Identificar un perfil de paciente incumplidor. MÉTODO: Estudio multicéntrico, observacional, prospectivo, de corte transversal, de una cohorte de adultos tratados al menos durante 6 meses con colistimetato de sodio (Promixin®) administrado con el nebulizador Ineb®. Se obtuvieron los registros del tratamiento nebulizado (plataforma informática Insight®), datos de función pulmonar, cultivos de esputo y número de agudizaciones antes y después del tratamiento. Se analizó la adherencia global, el manejo del nebulizador y la adherencia real. Se define a los pacientes con mala adherencia terapéutica como aquellos con una adherencia global o real ≤80%. RESULTADOS: La muestra inicial fue de 126 pacientes, considerándose no válidos para su análisis 20 de ellos, siendo seleccionados 106 pacientes con BQ no FQ, 47 de causa postinfecciosa (44,3%), 13 EPOC (12,3%), 12 discinesia ciliar (11,3%), 17 otras causas(16%) y 17 idiopáticas (16%). La edad media fue de 64,0 ± 14,6 años, 57 varones (53,8%) y 49 mujeres (46,2%), 61 procedentes de hospitales terciarios (57,5%) y 45 de comarcales (42,5%). La adherencia global fue del 86,7 ± 19,3% y en el 73,6% de los casos ≥80%. El 96,6 ± 7,8% de los pacientes manejaron adecuadamente el nebulizador, con unos tiempos de nebulización de 6,3 ± 3,4 minutos. La adherencia real fue del 84,4 ± 20,2% y en el 75,5% de los casos ≥80%. No hubo diferencias en cuanto al sexo, edad, función pulmonar, causa de las BQ no FQ y exacerbaciones previas para ninguna de estas variables. CONCLUSIÓN: En nuestra población el manejo del nebulizador y la adherencia, global y real, es muy buena. El escaso número de pacientes no adherentes no nos ha permitido definir el perfil del incumplidor

OBJECTIVE: 1) Assess adherence to nebulized treatment with colistimethate sodium-Promixin® using an Ineb® nebulizer in patients with bronchiectasis (BQ) but without cystic fibrosis (CF) colonized by Pseudomonas aeruginosa; 2) Identify a noncompliant patient profile. METHOD: A multi-center, observational, prospective, transversal study, with a cohort of adults treated for at least six months with colistimethate sodium (Promixin®) administered with an Ineb® nebulizer. Registers of nebulized treatment were obtained (Insight® IT platform), pulmonary lung function, sputum culture and number of exacerbations prior to and after the treatment. Global adherence was analyzed, as well as handling the nebulizer and real adherence. Patients with poor therapeutic adherence were defined as those with a global or real adherence of ≤80%. RESULTS: The initial sample included 126 patients, 20 of which were considered not valid for the analysis; 106 patients with BQ non-CF, 47 were post-infectious causes(44.3%), 13 COPD (12.3%), 12 ciliary dyskinesia(11.3%), 17 other causes (16%) and 17 idiopathic (16%). The mean age was 64.0 ± 14.6 years; 57 males (53.8%) and 49 females (46.2%), 61 were from tertiary hospitals (57.5%) and 45 from local hospitals (42.5%). Global adherence was 86.7 ± 19.3% and in 73.6% of the cases ≥80%. 96.6 ± 7.8% of the patients adequately handled the nebulizer, with nebulization times of 6.3 ± 3.4 minutes. Real adherence was 84.4 ± 20.2% and in 75.5% of the cases ≥80%. No differences were seen in terms of sex, age, pulmonary function, cause of BQ non-CF and prior exacerbations for none of these variables. CONCLUSION: In our population, handling the nebulizer and adherence, both global and real, is very good. The limited number of patients who failed to adhere has hindered our defining a non-compliant profile

Normative values of EQ-5D-5L: in a Spanish representative population sample from Spanish Health Survey, 2011.

PURPOSE: To derive EQ-5D-5L Spanish population norms based on a national representative sample adjusted by age, gender and region. METHODS: A representative sample of the Spanish general population (n = 21,007) was used in a cross-sectional study. The source of data was the Spanish National Health Survey 2011-2012. All socio-demographic factors and clinical characteristics were carried to a descriptive analysis. All variables were stratified by region, gender and age-group. RESULTS: The utility value 1 is the most repeated (62%) in this representative population sample. This study showed a deterioration of health states as age increases. Overall, men reported better health status than women. In relation to ceiling effect by regions, there was little difference with the highest scores. Conversely, the lowest score corresponds to Galicia. CONCLUSIONS: The paper reports EQ-5D-5L normative data for Spanish general population, based on a national representative sample adjusted by region, gender and age-group. These results may serve as reference data of the population health status. A regional difference in health status could be observed, which might suggest that policies aiming to reduce regional inequalities are important.

Loss of the tumor suppressor spinophilin (PPP1R9B) increases the cancer stem cell population in breast tumors.

The spinophilin (Spn, PPP1R9B) gene is located at 17q21.33, a region frequently associated with microsatellite instability and loss of heterozygosity, especially in breast tumors. Spn is a regulatory subunit of phosphatase1a (PP1), which targets the catalytic subunit to distinct subcellular locations. Spn downregulation reduces PPP1CA activity against the retinoblastoma protein, pRb, thereby maintaining higher levels of phosphorylated pRb. This effect contributes to an increase in the tumorigenic properties of cells in certain contexts. Here, we explored the mechanism of how Spn downregulation contributes to the malignant phenotype and poor prognosis in breast tumors and found an increase in the stemness phenotype. Analysis of human breast tumors showed that Spn mRNA and protein are reduced or lost in 15% of carcinomas, correlating with a worse prognosis, a more aggressive tumor phenotype and triple-negative tumors, whereas luminal tumors showed high Spn levels. Downregulation of Spn by shRNA increased the stemness properties along with the expression of stem-related genes (Sox2, KLF4, Nanog and OCT4), whereas ectopic overexpression of Spn cDNA reduced these properties. Breast tumor stem cells appeared to have low levels of Spn mRNA, and Spn loss correlated with increased stem-like cell appearance in breast tumors as indicated by an increase in CD44+/CD24- cells. A reduction of the levels of PPP1CA mimicked the cancer stem-like cell phenotype of Spn downregulation, suggesting that the mechanism of Spn involves PP1a. These increased cancer stem cell-like properties with reduced Spn might account for the malignant phenotype observed in Spn-loss tumors and may contribute to a worse patient prognosis.

The invasive potential of Giardia intestinalis in an in vivo model.

Giardiasis is a neglected parasitic disease that affects primarily children, in whom it delays physical and mental development. The pathophysiology of giardiasis in not well understood, and most reports have identified Giardia intestinalis trophozoites only in the lumen and on the brush border of the small intestine. We identified Giardia trophozoites within the epithelium of the small intestine of a lactose intolerance patient. The Giardia trophozoites were obtained and cultured in vitro. In addition, we demonstrated Giardia trophozoite invasion in an animal model. Giardia trophozoites invaded the intestinal mucosa and submucosa of infected gerbils. The invasive trophozoites were observed at 21, 30 and 60 days age, and the average numbers of invaded sites were 17 ± 5, 15 ± 4, and 9 ± 3, respectively. We found trophozoites between epithelial cells, at the base of empty goblet cells, in lacteal vessels and within the submucosa. The morphological integrity of the invasive trophozoites was demonstrated via electron microscopy. The analysis of the gerbils infected with the trophozoites of the WB reference strain did not show intraepithelial trophozoites. These results demonstrate another Giardia pathogenic mechanism, opening the door to numerous future studies.

Atomic monolayer deposition on the surface of nanotube mechanical resonators.

We study monolayers of noble gas atoms (Xe, Kr, Ar, and Ne) deposited on individual ultraclean suspended nanotubes. For this, we record the resonance frequency of the mechanical motion of the nanotube, since it provides a direct measure of the coverage. The latter is the number of adsorbed atoms divided by the number of the carbon atoms of the suspended nanotube. Monolayers form when the temperature is lowered in a constant pressure of noble gas atoms. The coverage of Xe monolayers remains constant at 1/6 over a large temperature range. This finding reveals that Xe monolayers are solid phases with a triangular atomic arrangement, and are commensurate with the underlying carbon nanotube. By comparing our measurements to theoretical calculations, we identify the phases of Ar and Ne monolayers as fluids, and we tentatively describe Kr monolayers as solid phases. These results underscore that mechanical resonators made from single nanotubes are excellent probes for surface science.

Polymer encapsulation of amoxicillin microparticles by SAS process.

Encapsulation of amoxicillin (AMC) with ethyl cellulose (EC) by a supercritical antisolvent process (SAS) was investigated. AMC microparticles obtained previously by an SAS process were used as host particles and EC, a biodegradable polymer used for the controlled release of drugs, was chosen as the coating material. In this work, a suspension of AMC microparticles in a solution of ethyl cellulose in dichloromethane (DCM) was sprayed through a nozzle into supercritical CO2. Scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS) and HPLC analyses were carried out. The effects of AMC:EC ratio, the initial polymer concentration of the solution, temperature and pressure on the encapsulation process were investigated. Although all the experiments led to powder precipitation, the AMC encapsulation was achieved in only half of the cases, particularly when the lower drug:polymer ratios were assayed. In general, it was observed that the percentages of AMC present in the precipitates were higher on increasing the AMC:EC ratio. In these cases composites rather than encapsulates were obtained. The in vitro release profiles of the resulting materials were evaluated in order to ascertain whether composites can be used as encapsulated systems for drug delivery systems.

Zero-temperature phase diagram of D2 physisorbed on graphane.

We determined the zero-temperature phase diagram of D2 physisorbed on graphane using the diffusion Monte Carlo method. The substrate used was C-graphane, an allotropic form of the compound that has been experimentally obtained through hydrogenation of graphene. We found that the ground state is the δ phase, a commensurate structure observed experimentally when D2 is adsorbed on graphite, and not the registered √3 x √3 structure characteristic of H2 on the same substrate.